Andersen, Mikael Rørdam

Casewell, Nicholas

Harrison, Robert

Laustsen, Andreas Hougaard

Pus, Urska

Each year, more than 5 million people worldwide are affected by a snakebite, resulting in 150,000 deaths, and 400,000 amputations. The current medical treatment against envenoming is based on the administration of an animal-derived antiserum, containing antibodies against snake venom toxins. Due to the heterologous and immunogenic nature of antivenom, patients in up to 80% of the cases experience serum sickness and anaphylaxis, which in some cases leads to death

Online Research Database In Technology

                       General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.  • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal   If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.     Downloaded from orbit.dtu.dk on: Dec 18, 2017Recombinant antivenoms based on mixtures of human antibodies against D. jamesonitoxinsPus, Urska; Harrison, Robert; Andersen, Mikael Rørdam; Casewell, Nicholas; Laustsen, AndreasHougaardPublication date:2016Document VersionPublisher's PDF, also known as Version of recordLink back to DTU OrbitCitation (APA):Pus, U., Harrison, R., Andersen, M. R., Casewell, N., & Laustsen, A. H. (2016). Recombinant antivenoms basedon mixtures of human antibodies against D. jamesoni toxins. Poster session presented at Symposium forBiological and Life Science Students (SymBLS) 2016, Cambridge, United Kingdom.Clinical manifestations of D. jamesoni toxinsEarly clinical signs• Paralysis• Fasciculation• Vertigo• Ataxia• Sudden loss of consciousnessLate clinical signs• Shock• Hypotension• Abdominal pain• Epistaxis• Pallor• Increased sweating• NauseaReferences[1] WHO, http://www.who.int/mediacentre/factsheets/fs337/en/[2] Gutierrez JM, Leon G, Lomonte B, Angulo Y. (2011) Antivenoms for snakebite envenomings. Inflammation & Allergy-Drug Targets 10(5): 369-80.[3] World Health Organization W. WHO guidelines for the production, control and regulation of snake antivenom immunoglobulins. Geneva: WHO, 2010; 134.[4] UCSD, http://toxicology.ucsd.edu/Snakebite%20Protocols/Dendroa2.htmContact informationDTU BioengeeringTechnical University of DenmarkSøltofts Plads 223DK-2800 Kgs. Lyngby, Denmarkrbc389@alumni.ku.dk/ (+386) 31 777 372AcknowledgementsWe thank the Novo Nordisk Foundation (NNF16OC0019248) and Symphogen A/S for financial support.Local tissue damage appears to be relatively infrequent and of minorseverity in most cases, whereas the accumulative effect of symptomsmay lead to death if not treated4.ToxicovenomicsSelection of scFvs by phage displayFormat conversion of scFv to IgGProduction of recombinant antibody mixturesPerspectivesThis project aims to develop a fully recombinant snakebiteantivenom against the potent venom of D. jamesoni. This antivenomwill be based on selected human IgG antibodies, compatible withthe human immune system and with proven specificity. It is theambition of this project to contribute to the development of safer,more effective, and inexpensive treatment options against snakebiteenvenoming.Venom collection HPLC SDS-PAGE Trypsin digestion MALDI-TOF-TOFVenom proteomeIn vivo toxicitytestingToxicity score1. Panning4. Elution5. AmplificationRepeatAnalyze6. ELISA2. Binding 3. Washing+ ++TOXIN TOX SCORETox A 110Tox B 37Tox C 11Tox D 5Target selectionscFvIgG scaffold Human IgGRecombinant antivenoms based on mixtures of human antibodies against D. jamesoni toxinsUrska Pus1, Mikael R. Andersen1, Robert Harrison2, Nicholas Casewell2, Andreas H. Laustsen11Department of Biotechnology and Biomedicine, Technical University of Denmark2Alistair Reid Venom Research Unit, Liverpool School of Tropical Medicine, Liverpool, United Kingdom The pressing problem of a snakebiteEach year, more than 5 million people worldwide are affected by asnakebite, resulting in 150,000 deaths, and 400,000 amputations1.The current medical treatment against envenoming is based on theadministration of an animal-derived antiserum, containingantibodies against snake venom toxins. Due to the heterologous andimmunogenic nature of antivenom, patients in up to 80% of thecases experience serum sickness and anaphylaxis, which in somecases leads to death2, 3.

Recombinant antivenoms based on mixtures of human antibodies against <i>D. jamesoni </i>toxins

http://orbit.dtu.dk/ws/files/127445271/Urska_W1.pdf

Recombinant antivenoms based on mixtures of human antibodies against <i>D. jamesoni </i>toxins

Abstract

Similar works

Full text

Available Versions

Online Research Database In Technology